Current treatment of solid tumors is limited by normal tissue tolerance, resulting in a narrow therapeutic index. To increase drug specificity and efficacy and to reduce toxicity in normal tissues, we have developed a polypeptide carrier for a cell cycle inhibitory peptide, which has the potential to be thermally targeted to the tumor site. The design of this polypeptide is based on elastin-like polypeptide (ELP). The coding sequence of ELP was modified by the addition of the cell penetrating peptide Bac-7 at the N-terminus and a 23 amino acid peptide derived from p21 at the C-terminus (Bac-ELP1-p21). Bac-ELP1-p21 is soluble in aqueous solutions below physiological temperature (37°C) but aggregates when the temperature is raised above 39°C, making it a promising thermally responsive therapeutic carrier that may be actively targeted to solid tumors by application of focused hyperthermia. While Bac-ELP1-p21 at 37°C did not have any effect on SKOV-3 cell proliferation, the use of hyperthermia increased the antiproliferative effect of Bac-ELP1-p21 compared with a thermally unresponsive control polypeptide. Bac-ELP1-p21 displayed both a cytoplasmic and nuclear distribution in the SKOV-3 cells, with nuclear-localized polypeptide enriched in the heated cells, as revealed by confocal microscopy. Using Western blotting, we show that Bac-ELP1-p21 caused a decrease in Rb phosphorylation levels in cells treated at 42°C. The polypeptide also induced caspase activation, PARP cleavage, and cell cycle arrest in S-phase and G2/M-phase. These studies indicate that ELP is a promising macromolecular carrier for the delivery of cell cycle inhibitory peptides to solid tumors.

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A seismic analysis of ground-supported, three-dimensional (3-D) rigid-base steel cylindrical liquid storage tank is investigated, using a coupled acoustic-structural finite element (FE) method for fluid-structure interaction (FSI). In this method, the contained liquid in the tank is modelled using acoustic elements and the cylindrical tank is modelled using shell elements. The impulsive and convective terms are estimated separately by using the appropriate boundary conditions on the free surface of the liquid. The convergence and validation studies of the proposed FE model are conducted by comparing the results reported in the literature. The parametric studies are performed for rigid and flexible tanks for the varying slenderness of the open roof tanks. The sloshing displacement and base shear time history responses are evaluated for the 3-D tanks subjected to harmonic unidirectional ground motions. Further, the results are compared with the commonly used two and three lumped-mass models of the tank. Moreover, the seismic response quantities of the tank subjected simultaneously to the bi-directional horizontal components of earthquake ground motion are also investigated using the 3-D FE model, and the response quantities are compared with the lumped-mass models. The results obtained from the 3-D FE model and lumped-mass model are in close agreement. The average percentage difference in the 3-D FE and lumped-mass models for maximum sloshing displacement prediction is 15 percent to 20 percent and that for the base shear is about 4 to 10 percent, in the case of the uni-directional harmonic ground motions. It is concluded that the sloshing displacement is not affected by the tank flexibility, but the impulsive hydrodynamic pressure and the impulsive component of the base shear increases with the tank flexibility.

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